The intent of this project is to develop an estrogen-deprivation model of age-related changes in lacrimal gland function, to assess the role of two peptidergic hormones, ACTH and prolactin, in lacrimal gland secretion, and to describe any interactions between autonomic and peptidergic control of lacrimal gland function and hormonal status. Proteins secreted by the lacrimal gland contribute to the formation of tears and disruption of gland function results in corneal drying which may lead to deterioration and blindness. Tear insufficiency is found in older patients, especially in women. The development of a model which will isolate one age-related factor, hormonal status, is proposed. Furthermore, the role in lacrimal secretion of ACTH and prolactin, two hormones found in the human lacrimal gland, will be assessed. Three month of old Fischer 344 rats will be ovriectomized and three weeks later will receive estrogen or placebo implants. One week following this, baseline responses and the response to secretagogues will be measured in lacrimal gland fragments. Fragments will be perifused with carbachol or phenylephrine, known autonomic agonists, or with ACTH or prolactin. Secreted protein and peroxidase activity will be measured. In separate experiments, lacrimal gland fragments will be incubated in the presence of ACTH and intracellular cAMP will be measured by radioimmunoassay. These experiments will allow the determination of the effects of estrogen on lacrimal gland function and of any interaction of estrogen with secretagogues of the lacrimal gland. A better understanding of the dependence of the lacrimal gland on estrogen may provide new insight for the development of therapy for age-related dry eyes in women.